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Is it better to 'contain' rather than destroy cancer?

A new approach to cancer therapy suggests that doctors may be able to keep cancer in check by placing metastatic cells in a state of dormancy, thus blocking them from giving rise to new tumors. A recent study in mice has found that an existing drug could effectively contain metastatic breast cancer cells.

A minimally toxic drug could help stop cancer from metastasizing, but clinical trials may be a long way off.

"Most cancer therapy is targeted with the idea that we want to kill all of the cancer cells. Rid the body of cancer," says Michael Wendt, an assistant professor at Purdue University, in West Lafayette, IN.

However, the researcher — who specializes in the treatment of metastatic cancer — explains that this approach may not be feasible.

"Recently," Wendt notes, "there are lots of studies that suggest that we're never going to be able to do that. Cancer cells evolve so fast that they will always find a way to overcome any type of therapy."

Because of this, Wendt and a team of scientists from Purdue University and other academic institutions have decided to experiment with a different approach to treating cancer: that of safely containing it and blocking it from developing and spreading.

"An emerging concept in cancer treatment is that maybe we shouldn't try to kill all of the cancer cells, but try to keep them in a low state that doesn't generate any kind of symptoms. A sort of dormancy, if you will," Wendt explains.

In the new study — the findings of which appear in the journal Cancer Research — the investigators used an existing drug to stop metastatic breast cancer cells from giving rise to new tumors by keeping them in a sleep-like state.

Existing drug can block stray cancer cells

The researchers zeroed in on the drug fostamatinib, which is currently approved for the treatment of immune thrombocytopenia, an autoimmune disease characterized by a low platelet count in the blood.

The team explains that their research in mice has shown that fostamatinib is also able to contain metastatic cancer cells and stop them from developing into full tumors, causing further damage.

First author Aparna Shinde, Ph.D. — a former graduate student at Purdue and now a researcher at AbbVie, a biopharmaceutical company — in collaboration with Wendt and the team, looked at whether they could block metastatic breast cancer cells.

That is because, Shinde explains, breast cancer cells can spread to other parts of the body, where they can enter a latent state for many years, escaping detection.

Once awakened, these metastatic cells give rise to new and sometimes more aggressive and less treatable tumors, marking the return of the cancer a long time after the treatment of the primary tumors.

"After you have breast cancer, you always get this dissemination of cancer cells. Breast cancer is no longer considered a curable disease — it is now considered a chronic disease because 10 or 20 years later, you can get secondary tumors because of the metastasizing cells," says Shinde.

Such cells often do not respond to existing therapies, and for this reason, Shinde and team thought that it could be more useful to try to contain the cells and block their development, rather than attempt to destroy them altogether.

"So that's the goal we are exploring now," Wendt observes, noting that the study authors' research question has been, "Instead of trying to eliminate those disseminated cells, how do we keep them in that dormant state?"

'Very difficult' to organize clinical trials

Shinde, Wendt, and colleagues went on to experiment with fostamatinib because they knew that the drug inhibits the activity of spleen tyrosine kinase, a protein present in latent metastatic cancer cells.

Working with mouse models of breast cancer, the researchers found that, when they treated metastatic cancer cells with this drug, those cells remained contained and did not give rise to new tumors.

"This is great for us because this is a drug with low toxicity. It's designed for people with chronic disease so that they can take [it] for a long time. So we think fostamatinib is a perfect candidate for this kind of years-long lock-'n'-block type of approach."

Aparna Shinde, Ph.D.

"We think this is a good candidate to move forward for a trial to see if we can stabilize dormancy. If [spleen tyrosine kinase] is expressed in other cancers, this could apply to those as well," Shinde hypothesizes.

However, while the researchers are happy about their current findings and the promising implications for future therapeutic strategies, they note that it may be difficult to test this approach further, in clinical trials.

"Our work is unique because there hasn't been much research that tests treatments in a postsurgical metastatic setting," says Wendt.

"But you can imagine that [setting up] clinical trials for this kind of thing is going to be very difficult because, technically, the patients are in remission and disease-free," he adds.

"We suspect that these patients have these dormant cancer cells disseminating through their bodies, but we don't have a way to detect those right now," he goes on, suggesting that the road toward marking fostamatinib as a new therapeutic option for cancer may be long and difficult.

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